Exocrine pancreas trans-differentiation to hepatocytes—A physiological response to elevated glucocorticoid in vivo

Glucocorticoid-dependent transdifferentiation of pancreatic progenitor cells into hepatocytes is dependent on transient suppression of WNT signalling

“…It was first shown to express liver-specific genes, such as albumin, in response to glucocorticoid treatment several years later by Shen et al (Shen et al, 2000). Subsequent investigations have demonstrated that the B-13 cell undergoes widespread coordinated differentiation into hepatocyte-like cells that are qualitatively and quantitatively functionally comparable to freshly isolated rat hepatocytes (Shen et al, 2000;Marek et al, 2003;Lardon et al, 2004;Wallace et al, 2009). An important question regarding the B-13 cell response to glucocorticoid is whether it is relevant to any real physiological response in the embryo, developing foetus or adult.…”

“…Control cells were treated with ethanol alone. Typically, 85% of B-13 cells transdifferentiated into B-13/H cells with continuous DEX treatment, as judged by phenotypic observation (see Wallace et al, 2009). Maximal transdifferentiation occurred after 10-14 days treatment, with further treatment not increasing the proportion of transdifferentiated cells.…”

Disrupted Pancreatic Exocrine Differentiation and Malabsorption in Response to Chronic Elevated Systemic Glucocorticoid

“…20 Antibodies were obtained from local commercial suppliers as previously reported 17,20 except anti-cyp3a25, which was generously provided by Dr. Rob Edwards (Imperial College, London, UK).…”

“…17,21 All cells were incubated at 37°C in an humidified incubator gassed with 5% CO 2 in air. Dexamethasone (DEX), human corticotropin releasing hormone (CRH, identical to rat sequence except for an additional N-terminal 3 amino acids), and adrenocorticotropic hormone (ACTH, a truncated 1-24 peptide sequence conserved between human, rat, and mouse was used, which shows 85% activity of the full length peptide sequence) were all purchased from the Sigma Chem Co. (Poole, UK) and were added to medium from 1000-fold concentrated ethanol vehicle solvated stocks.…”

“…10 Nonphysiological elevated levels of systemic glucocorticoids also inhibit inflammation, 11 which is used therapeutically in the treatment of a range of chronic inflammatory diseases, including ulcerative colitis, 12 Crohn's disease, 13 asthma, 14 autoimmune hepatitis, 15 rheumatoid arthritis, 16 and others. We have recently demonstrated that treating rats for 25 days with the synthetic glucocorticoid dexamethasone resulted in the occasional appearance of exocrine cells expressing hepatic mark-ers, 17 suggesting that acinar cells may also transdifferentiate into hepatocyte-like cells in vivo in response to elevated glucocorticoid.…”